International Journal of Molecular Sciences

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18 pages, 4483 KiB

Open AccessArticle

Effect of Fibrin Concentration on the In Vitro Production of Dermo-Epidermal Equivalents

by Andrés Montero, Cristina Quílez, Leticia Valencia, Paula Girón, José Luis Jorcano and Diego Velasco

Int. J. Mol. Sci. 2021, 22(13), 6746; https://doi.org/10.3390/ijms22136746 - 23 Jun 2021

Cited by 12 | Viewed by 3657

Abstract

Human plasma-derived bilayered skin substitutes were successfully used by our group to produce human-based in vitro skin models for toxicity, cosmetic, and pharmaceutical testing. However, mechanical weakness, which causes the plasma-derived fibrin matrices to contract significantly, led us to attempt to improve their [...] Read more.

Human plasma-derived bilayered skin substitutes were successfully used by our group to produce human-based in vitro skin models for toxicity, cosmetic, and pharmaceutical testing. However, mechanical weakness, which causes the plasma-derived fibrin matrices to contract significantly, led us to attempt to improve their stability. In this work, we studied whether an increase in fibrin concentration from 1.2 to 2.4 mg/mL (which is the useful fibrinogen concentration range that can be obtained from plasma) improves the matrix and, hence, the performance of the in vitro skin cultures. The results show that this increase in fibrin concentration indeed affected the mechanical properties by doubling the elastic moduli and the maximum load. A structural analysis indicated a decreased porosity for the 2.4 mg/mL hydrogels, which can help explain this mechanical behavior. The contraction was clearly reduced for the 2.4 mg/mL matrices, which also allowed for the growth and proliferation of primary fibroblasts and keratinocytes, although at a somewhat reduced rate compared to the 1.2 mg/mL gels. Finally, both concentrations of fibrin gave rise to organotypic skin cultures with a fully differentiated epidermis, although their lifespans were longer (25–35%) in cultures with more concentrated matrices, which improves their usefulness. These systems will allow the generation of much better in vitro skin models for the testing of drugs, cosmetics and chemicals, or even to “personalized” skin for the diagnosis or determination of the most effective treatment possible. Full article

(This article belongs to the Special Issue Advanced Biomaterials for Wound Healing 2021)

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18 pages, 6234 KiB

Open AccessArticle

Cytocompatibility and Suitability of Protein-Based Biomaterials as Potential Candidates for Corneal Tissue Engineering

by Cristina Romo-Valera, Pedro Guerrero, Jon Arluzea, Jaime Etxebarria, Koro de la Caba and Noelia Andollo

Int. J. Mol. Sci. 2021, 22(7), 3648; https://doi.org/10.3390/ijms22073648 - 31 Mar 2021

Cited by 10 | Viewed by 3054

Abstract

The vision impairments suffered by millions of people worldwide and the shortage of corneal donors show the need of substitutes that mimic native tissue to promote cell growth and subsequent tissue regeneration. The current study focused on the in vitro assessment of protein-based [...] Read more.

The vision impairments suffered by millions of people worldwide and the shortage of corneal donors show the need of substitutes that mimic native tissue to promote cell growth and subsequent tissue regeneration. The current study focused on the in vitro assessment of protein-based biomaterials that could be a potential source for corneal scaffolds. Collagen, soy protein isolate (SPI), and gelatin films cross-linked with lactose or citric acid were prepared and physicochemical, transmittance, and degradation measurements were carried out. In vitro cytotoxicity, cell adhesion, and migration studies were performed with human corneal epithelial (HCE) cells and 3T3 fibroblasts for the films’ cytocompatibility assessment. Transmittance values met the cornea’s needs, and the degradation profile revealed a progressive biomaterials’ decomposition in enzymatic and hydrolytic assays. Cell viability at 72 h was above 70% when exposed to SPI and gelatin films. Live/dead assays and scanning electron microscopy (SEM) analysis demonstrated the adhesion of both cell types to the films, with a similar arrangement to that observed in controls. Besides, both cell lines were able to proliferate and migrate over the films. Without ruling out any material, the appropriate optical and biological properties shown by lactose-crosslinked gelatin film highlight its potential for corneal bioengineering. Full article

(This article belongs to the Special Issue Advanced Biomaterials for Wound Healing 2021)

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18 pages, 4213 KiB

Open AccessArticle

Accelerated Wound Closure of Deep Partial Thickness Burns with Acellular Fish Skin Graft

by Randolph Stone II, Emily C. Saathoff, David A. Larson, John T. Wall, Nathan A. Wienandt, Skuli Magnusson, Hilmar Kjartansson, Shanmugasundaram Natesan and Robert J. Christy

Int. J. Mol. Sci. 2021, 22(4), 1590; https://doi.org/10.3390/ijms22041590 - 4 Feb 2021

Cited by 50 | Viewed by 10089

Abstract

Thermal injuries are caused by exposure to a variety of sources, and split thickness skin grafts are the gold standard treatment for severe burns; however, they may be impossible when there is no donor skin available. Large total body surface area burns leave [...] Read more.

Thermal injuries are caused by exposure to a variety of sources, and split thickness skin grafts are the gold standard treatment for severe burns; however, they may be impossible when there is no donor skin available. Large total body surface area burns leave patients with limited donor site availability and create a need for treatments capable of achieving early and complete coverage that can also retain normal skin function. In this preclinical trial, two cellular and tissue based products (CTPs) are evaluated on twenty-four 5 × 5 deep partial thickness (DPT) burn wounds. Using appropriate pain control methods, DPT burn wounds were created on six anesthetized Yorkshire pigs. Wounds were excised one day post-burn and the bleeding wound beds were subsequently treated with omega-3-rich acellular fish skin graft (FSG) or fetal bovine dermis (FBD). FSG was reapplied after 7 days and wounds healed via secondary intentions. Digital images, non-invasive measurements, and punch biopsies were acquired during rechecks performed on days 7, 14, 21, 28, 45, and 60. Multiple qualitative measurements were also employed, including re-epithelialization, contraction rates, hydration, laser speckle, and trans-epidermal water loss (TEWL). Each treatment produced granulated tissue (GT) that would be receptive to skin grafts, if desired; however, the FSG induced GT 7 days earlier. FSG treatment resulted in faster re-epithelialization and reduced wound size at day 14 compared to FBD (50.2% vs. 23.5% and 93.1% vs. 106.7%, p < 0.005, respectively). No differences in TEWL measurements were observed. The FSG integrated into the wound bed quicker as evidenced by lower hydration values at day 21 (309.7 vs. 2500.4 µS, p < 0.05) and higher blood flow at day 14 (4.9 vs. 3.1 fold change increase over normal skin, p < 0.005). Here we show that FSG integrated faster without increased contraction, resulting in quicker wound closure without skin graft application which suggests FSG improved burn wound healing over FBD. Full article

(This article belongs to the Special Issue Advanced Biomaterials for Wound Healing 2021)

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10 pages, 3058 KiB

Open AccessArticle

Ibudilast Mitigates Delayed Bone Healing Caused by Lipopolysaccharide by Altering Osteoblast and Osteoclast Activity

by Yuhan Chang, Chih-Chien Hu, Ying-Yu Wu, Steve W. N. Ueng, Chih-Hsiang Chang and Mei-Feng Chen

Int. J. Mol. Sci. 2021, 22(3), 1169; https://doi.org/10.3390/ijms22031169 - 25 Jan 2021

Cited by 11 | Viewed by 3197

Abstract

Bacterial infection in orthopedic surgery is challenging because cell wall components released after bactericidal treatment can alter osteoblast and osteoclast activity and impair fracture stability. However, the precise effects and mechanisms whereby cell wall components impair bone healing are unclear. In this study, [...] Read more.

Bacterial infection in orthopedic surgery is challenging because cell wall components released after bactericidal treatment can alter osteoblast and osteoclast activity and impair fracture stability. However, the precise effects and mechanisms whereby cell wall components impair bone healing are unclear. In this study, we characterized the effects of lipopolysaccharide (LPS) on bone healing and osteoclast and osteoblast activity in vitro and in vivo and evaluated the effects of ibudilast, an antagonist of toll-like receptor 4 (TLR4), on LPS-induced changes. In particular, micro-computed tomography was used to reconstruct femoral morphology and analyze callus bone content in a femoral defect mouse model. In the sham-treated group, significant bone bridge and cancellous bone formation were observed after surgery, however, LPS treatment delayed bone bridge and cancellous bone formation. LPS inhibited osteogenic factor-induced MC3T3-E1 cell differentiation, alkaline phosphatase (ALP) levels, calcium deposition, and osteopontin secretion and increased the activity of osteoclast-associated molecules, including cathepsin K and tartrate-resistant acid phosphatase in vitro. Finally, ibudilast blocked the LPS-induced inhibition of osteoblast activation and activation of osteoclast in vitro and attenuated LPS-induced delayed callus bone formation in vivo. Our results provide a basis for the development of a novel strategy for the treatment of bone infection. Full article

(This article belongs to the Special Issue Advanced Biomaterials for Wound Healing 2021)

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14 pages, 6902 KiB

Open AccessArticle

Processed Eggshell Membrane Powder Is a Promising Biomaterial for Use in Tissue Engineering

by Sissel B. Rønning, Ragnhild S. Berg, Vibeke Høst, Eva Veiseth-Kent, Christian R. Wilhelmsen, Eirik Haugen, Henri-Pierre Suso, Paul Barham, Ralf Schmidt and Mona E. Pedersen

Int. J. Mol. Sci. 2020, 21(21), 8130; https://doi.org/10.3390/ijms21218130 - 30 Oct 2020

Cited by 12 | Viewed by 4128

Abstract

The purpose of this study was to investigate the tissue regenerating and biomechanical properties of processed eggshell membrane powder (PEP) for use in 3D-scaffolds. PEP is a low-cost, natural biomaterial with beneficial bioactive properties. Most importantly, this material is available as a by-product [...] Read more.

The purpose of this study was to investigate the tissue regenerating and biomechanical properties of processed eggshell membrane powder (PEP) for use in 3D-scaffolds. PEP is a low-cost, natural biomaterial with beneficial bioactive properties. Most importantly, this material is available as a by-product of the chicken egg processing (breaking) industry on a large scale, and it could have potential as a low-cost ingredient for therapeutic scaffolds. Scaffolds consisting of collagen alone and collagen combined with PEP were produced and analyzed for their mechanical properties and the growth of primary fibroblasts and skeletal muscle cells. Mechanical testing revealed that a PEP/collagen-based scaffold increased the mechanical hardness of the scaffold compared with a pure collagen scaffold. Scanning electron microscopy (SEM) demonstrated an interconnected porous structure for both scaffolds, and that the PEP was evenly distributed in dense clusters within the scaffold. Fibroblast and skeletal muscle cells attached, were viable and able to proliferate for 1 and 2 weeks in both scaffolds. The cell types retained their phenotypic properties expressing phenotype markers of fibroblasts (TE7, alpha-smooth muscle actin) and skeletal muscle (CD56) visualized by immunostaining. mRNA expression of the skeletal muscle markers myoD, myogenin, and fibroblasts marker (SMA) together with extracellular matrix components supported viable phenotypes and matrix-producing cells in both types of scaffolds. In conclusion, PEP is a promising low-cost, natural biomaterial for use in combination with collagen as a scaffold for 3D-tissue engineering to improve the mechanical properties and promote cellular adhesion and growth of regenerating cells. Full article

(This article belongs to the Special Issue Advanced Biomaterials for Wound Healing 2021)

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12 pages, 4404 KiB

Open AccessArticle

Bioshell Calcium Oxide (BiSCaO) Ointment for the Disinfection and Healing of Pseudomonas aeruginosa-Infected Wounds in Hairless Rats

by Tomohiro Takayama, Masayuki Ishihara, Shingo Nakamura, Yoko Sato, Sumiyo Hiruma, Koichi Fukuda, Kaoru Murakami and Hidetaka Yokoe

Int. J. Mol. Sci. 2020, 21(11), 4176; https://doi.org/10.3390/ijms21114176 - 11 Jun 2020

Cited by 8 | Viewed by 3693

Abstract

Bioshell calcium oxide (BiSCaO) possesses deodorizing properties and broad microbicidal activity. This study aimed to investigate the application of BiSCaO ointment for the prevention and treatment of infection in chronic wounds in healing-impaired patients, without delaying wound healing. The bactericidal activities of 0.04, [...] Read more.

Bioshell calcium oxide (BiSCaO) possesses deodorizing properties and broad microbicidal activity. This study aimed to investigate the application of BiSCaO ointment for the prevention and treatment of infection in chronic wounds in healing-impaired patients, without delaying wound healing. The bactericidal activities of 0.04, 0.2, 1, and 5 wt% BiSCaO ointment, 3 wt% povidone iodine ointment, and control (ointment only) were compared to evaluate the in vivo disinfection and healing of Pseudomonas aeruginosa-infected wounds in hairless rats. Treatment of the infected wounds with 0.2 wt% BiSCaO ointment daily for 3 days significantly enhanced wound healing and reduced the in vivo bacterial counts compared with povidone iodine ointment and control (no wound cleaning). Although 5 wt% BiSCaO ointment provided the lowest bacterial counts during 3 days’ treatment, it delayed wound healing. Histological examinations showed significantly advanced granulation tissue and capillary formation in wounds treated with 0.2 wt% BiSCaO ointment for 3 days compared to wounds treated with the other ointments. This study suggested that using 0.2 wt% BiSCaO ointment as a disinfectant for infected wounds and limiting disinfection to 3 days may be sufficient to avoid the negative effects of BiSCaO on wound repair. Full article

(This article belongs to the Special Issue Advanced Biomaterials for Wound Healing 2021)

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Review

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28 pages, 2508 KiB

Open AccessReview

Nanoceutical Adjuvants as Wound Healing Material: Precepts and Prospects

by Kaushita Banerjee, Radha Madhyastha, Yuichi Nakajima, Masugi Maruyama and Harishkumar Madhyastha

Int. J. Mol. Sci. 2021, 22(9), 4748; https://doi.org/10.3390/ijms22094748 - 29 Apr 2021

Cited by 29 | Viewed by 6545

Abstract

Dermal wound healing describes the progressive repair and recalcitrant mechanism of 12 damaged skin, and eventually, reformatting and reshaping the skin. Many probiotics, nutritional supplements, metal nanoparticles, composites, skin constructs, polymers, and so forth have been associated with the improved healing process of [...] Read more.

Dermal wound healing describes the progressive repair and recalcitrant mechanism of 12 damaged skin, and eventually, reformatting and reshaping the skin. Many probiotics, nutritional supplements, metal nanoparticles, composites, skin constructs, polymers, and so forth have been associated with the improved healing process of wounds. The exact mechanism of material-cellular interaction is a point of immense importance, particularly in pathological conditions such as diabetes. Bioengineered alternative agents will likely continue to dominate the outpatient and perioperative management of chronic, recalcitrant wounds as new products continue to cut costs and improve the wound healing process. This review article provides an update on the various remedies with confirmed wound healing activities of metal-based nanoceutical adjuvanted agents and also other nano-based counterparts from previous experiments conducted by various researchers. Full article

(This article belongs to the Special Issue Advanced Biomaterials for Wound Healing 2021)

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25 pages, 2283 KiB

Open AccessReview

Exploration of Bioengineered Scaffolds Composed of Thermo-Responsive Polymers for Drug Delivery in Wound Healing

by Luis Castillo-Henríquez, Jose Castro-Alpízar, Mary Lopretti-Correa and José Vega-Baudrit

Int. J. Mol. Sci. 2021, 22(3), 1408; https://doi.org/10.3390/ijms22031408 - 30 Jan 2021

Cited by 45 | Viewed by 6769

Abstract

Innate and adaptive immune responses lead to wound healing by regulating a complex series of events promoting cellular cross-talk. An inflammatory response is presented with its characteristic clinical symptoms: heat, pain, redness, and swelling. Some smart thermo-responsive polymers like chitosan, polyvinylpyrrolidone, alginate, and [...] Read more.

Innate and adaptive immune responses lead to wound healing by regulating a complex series of events promoting cellular cross-talk. An inflammatory response is presented with its characteristic clinical symptoms: heat, pain, redness, and swelling. Some smart thermo-responsive polymers like chitosan, polyvinylpyrrolidone, alginate, and poly(ε-caprolactone) can be used to create biocompatible and biodegradable scaffolds. These processed thermo-responsive biomaterials possess 3D architectures similar to human structures, providing physical support for cell growth and tissue regeneration. Furthermore, these structures are used as novel drug delivery systems. Locally heated tumors above the polymer lower the critical solution temperature and can induce its conversion into a hydrophobic form by an entropy-driven process, enhancing drug release. When the thermal stimulus is gone, drug release is reduced due to the swelling of the material. As a result, these systems can contribute to the wound healing process in accelerating tissue healing, avoiding large scar tissue, regulating the inflammatory response, and protecting from bacterial infections. This paper integrates the relevant reported contributions of bioengineered scaffolds composed of smart thermo-responsive polymers for drug delivery applications in wound healing. Therefore, we present a comprehensive review that aims to demonstrate these systems’ capacity to provide spatially and temporally controlled release strategies for one or more drugs used in wound healing. In this sense, the novel manufacturing techniques of 3D printing and electrospinning are explored for the tuning of their physicochemical properties to adjust therapies according to patient convenience and reduce drug toxicity and side effects. Full article

(This article belongs to the Special Issue Advanced Biomaterials for Wound Healing 2021)

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